Document Detail


Competition between innate multidrug resistance and intracellular binding of rhodamine dyes.
MedLine Citation:
PMID:  19120455     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The present study aimed to elucidate the contribution of the intracellular binding of drugs to multidrug resistance. For this purpose, uptake of rhodamines was studied in cells whose mitochondria had been uncoupled with carbonyl cyanide m-chlorophenylhydrazone. Surprisingly, in a variety of drug-untreated cells, presumed to be sensitive to multidrug resistance-type drugs, rhodamines were excluded from entering the cells. Thus, the amount of rhodamine 123 taken up into parental untreated K562 cells was less than the amount bound to the cell exterior. Rhodamine uptake was prevented by an active efflux pump. The efflux was inhibited by 4-chloro-7-nitro-2,1,3-benzoxadiazole (NBD-Cl) and MK571 and, to a lesser extent, by ATP depletion, indomethacin, probenecid and vanadate. All the inhibitors, apart from NBD-Cl, are known to modulate multidrug resistance-associated protein (MRP) 1. Because MRP1 was expressed in all the cell lines tested and the efflux of rhodamines in MRP1 over-expressing cells was abolished by NBD-Cl, it appears that rhodamines are excluded from these cells by MRP1. On the other hand, the uptake of rhodamines into cells respiring with their coupled mitochondria demonstrated diminished sensitivity to NBD-Cl and MK571. Thus, active pumping into the mitochondria allowed enhanced uptake into the cells, overcoming the innate resistance. The innate resistance provided by MRP1 to cells prevents rhodamine dyes, and possibly drugs such as doxorubicin, from achieving equilibration of their concentration in the cytoplasm with their concentration in the external medium. The protection provided to multidrug resistance cells by ABC transporters has to overcome competition by passive uptake of the drugs and binding/uptake of the drugs into intracellular targets.
Authors:
Daniella Yeheskely-Hayon; Ronit Regev; Hagar Katzir; Gera D Eytan
Related Documents :
1917165 - Induction of multiple-drug resistance during anti-neoplastic chemotherapy in vitro.
1998955 - The multidrug resistance phenotype: 31p nuclear magnetic resonance characterization and...
7706385 - Drug efflux mediated by the human multidrug resistance p-glycoprotein is inhibited by c...
7488425 - Flow cytometric functional analysis of multidrug resistance by fluo-3: a comparison wit...
10923635 - Linear correlation between beta-cell mass and body weight throughout the lifespan in le...
18582455 - Bucky ball functions in balbiani body assembly and animal-vegetal polarity in the oocyt...
Publication Detail:
Type:  Journal Article     Date:  2008-12-12
Journal Detail:
Title:  The FEBS journal     Volume:  276     ISSN:  1742-4658     ISO Abbreviation:  FEBS J.     Publication Date:  2009 Feb 
Date Detail:
Created Date:  2009-01-15     Completed Date:  2009-02-10     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101229646     Medline TA:  FEBS J     Country:  England    
Other Details:
Languages:  eng     Pagination:  637-48     Citation Subset:  IM    
Affiliation:
Department of Biology, The Technion-Israel Institute of Technology, Haifa, Israel.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Drug Resistance, Multiple*
Fluorescent Dyes / chemistry*,  metabolism
Humans
K562 Cells
Kinetics
Rhodamines / chemistry*,  metabolism
Chemical
Reg. No./Substance:
0/Fluorescent Dyes; 0/Rhodamines; 0/tetramethylrhodamine methyl ester

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Regulators of G-protein signalling are modulated by bacterial lipopeptides and lipopolysaccharide.
Next Document:  Advantages and limitations of quantitative PCR (Q-PCR)-based approaches in microbial ecology.